An analysis of genetic data from over 900,000 people shows that certain stretches of DNA, made up of short sequences repeated over and over, become longer and more unstable as we age. The study found that common genetic variants can speed up or slow down this process by up to four-fold, and that certain expanded sequences are linked to serious diseases including kidney failure and liver disease.
More than 60 inherited disorders are caused by expanded DNA repeats: repetitive genetic sequences that grow longer over time. These include devastating conditions like Huntington’s disease, myotonic dystrophy, and certain forms of ALS.
Most people carry DNA repeats that gradually expand throughout their lives, but this instability and what genetic factors control it hadn’t been fully analyzed within large biobanks.
1Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA.
2Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Address correspondence to: Laura D. Attardi, Stanford University School of Medicine, 269 Campus Drive, CCSR-South, Room 1,255, Stanford, California, 94,305, USA. Phone: 650.725.8424; Email: attardi@stanford.edu.
IDH-mutant glioma, caused by abnormalities in a specific gene (IDH), is the most common malignant brain tumor among young adults under the age of 50. It is a refractory brain cancer that is difficult to treat due to its high recurrence rate.
Until now, treatment has focused primarily on removing the visible tumor mass. However, a Korean research team has discovered for the first time that normal brain cells acquire the initial IDH mutation and spread out through the cortex long before a visible tumor mass harboring additional cancer mutations forms, opening a new path for early diagnosis and treatment to suppress recurrence.
As species evolve, random genetic mutations arise. Some of these mutations become fixed, meaning they spread until every individual in a population carries the change. The Neutral Theory of Molecular Evolution argues that most mutations that reach this stage are neutral. Harmful mutations are quickly eliminated, while helpful ones are assumed to be extremely rare, explains evolutionary biologist Jianzhi Zhang.
Zhang and his colleagues set out to test whether this idea holds up when examined more closely. Their results pointed to a major problem. The researchers found that beneficial mutations occur far more often than the Neutral Theory allows. At the same time, they observed that the overall rate at which mutations become fixed in populations is much lower than would be expected if so many helpful mutations were taking hold.
Statins in genetic myopathies: a retrospective analysis of safety and tolerability.
ObjectivesStatins are widely prescribed lipid-lowering agents, but their safety and tolerability in patients with underlying genetic myopathies remain uncertain. We aimed to study statin safety and tolerability in genetic myopathies using a large retrospective cohort.
Novel research led by Brazilian scientists describes the immune system’s reactions in detail in the first living patient to receive a genetically modified pig kidney transplant. This paves the way for the search for therapies that can prevent organ rejection.
The study demonstrates the feasibility of this type of graft but indicates that controlling initial rejection alone is insufficient. This is because even with immunosuppressants, continuous activation of innate immunity—the body’s first line of defense, especially macrophages, which react to any threat—can compromise long-term survival.
Through transcriptomic, proteomic, metabolomic, and spatial analyses, the scientists have determined that new strategies are necessary to achieve long-term survival and favorable clinical outcomes. They recommend combining therapies that target innate immunity with advanced genetic engineering in donor pigs. They also suggest preventing early T lymphocyte-mediated rejection and implementing more sensitive monitoring approaches.
Precision and timing of gene expression is essential for normal biological functions and, when disrupted, can lead to many human diseases, including cancers. However, how molecular machines—protein complexes—that control gene expression locate to specific genes at specific times within the nuclei of our cells has remained a mystery.
Now, scientists at Dana-Farber Cancer Institute have discovered a new protein domain, SWIFT, found on a major chromatin remodeling complex family called mammalian SWI/SNF (mSWI/SNF or BAF) complexes, which helps these regulatory machines target particular genes to activate their expression.
The findings, published in Science, reveal how the SWIFT platform on mSWI/SNF complexes engage transcription factors (TF) to enable specialized cellular functions during both normal development and cancer. Particularly in human cancers, SWIFT-TF engagement sustains cancer-promoting gene expression and cell growth. Notably, breaking interactions with mutations halts cancer cell growth, flagging this new SWIFT-TF platform as a promising target for small molecule development.
Oral PCSK9 Therapy And The Future Of Heart Disease — Dr. Christie Ballantyne MD, Director, Center for Cardiometabolic Disease Prevention, Baylor College of Medicine & Dr. Alexander Tal, MD.
Dr. Christie M. Ballantyne, MD is a Cardiologist and is one of the nation’s foremost experts on lipids, atherosclerosis and heart disease prevention. He holds many leadership positions at Baylor College of Medicine (https://www.bcm.edu/people-search/chr… including director of the Center for Cardiometabolic Disease Prevention, co-director of the Lipid Metabolism and Atherosclerosis Clinic, and chief of the Section of Cardiology.
With over 1,000 publications in the area of atherosclerosis, lipids, and inflammation, Dr. Ballantyne’s research on heart disease prevention has led him to become an established investigator for the American Heart Association and the recipient of continuous funding from the National Institutes of Health with a core focus on in basic research of leukocyte–endothelial interactions, translational research in biomarkers, and clinical trials.
Dr. Ballantyne’s many accomplishments have included being elected as Fellow of the American Association for the Advancement of Science, the American Society of Clinical Investigation, and the Association of American Physicians. In 2012, he received the American College of Cardiology Distinguished Scientist Award (Basic Domain).
In 2014 and 2015, Thomson Reuters recognized Dr. Ballantyne as one of “The World’s Most Influential Scientific Minds.” Clarivate Analytics, Web of Science, named Dr. Ballantyne as a “Highly Cited Researcher” 2017–2022 in the top 1% of researchers most cited.
Their in-depth DNA analysis also showed that resident killer whales shared the same haplotype (group of inherited genes) while the transients had eight different haplotypes making them more genetically diverse. This finding suggests that transient killer whales used Hokkaido as a refuge during the last Ice Age, the researchers say.
“Clarifying the ecological characteristics of killer whales is crucial for achieving coexistence with them,” says first author Momoka Suzuki, Kyoto University, in a statement.
Understanding the diet and behaviour of orcas in Japanese waters gives conservationists important information that can help protect the animals from threats. “They are deeply entwined with human activities such as tourism and fisheries in Hokkaido,” adds Suzuki.
Exciting to see this modern genomic approach to classification of psychiatric disorders! Hopefully this will eventually lead to potential new gene therapy targets for treatment.
Analysis of more than one million people shows that mental-health disorders fall into five clusters, each of them linked to a specific set of genetic variants.
